Trigeminal Sensory Nuclear Complex Research Articles

Effects of Peripheral Nerve Injury on the Induction of c-Fos and Phosphorylated ERK in the Brainstem Trigeminal Sensory Nuclear Complex.

Sequential changes in brainstem and spinal cord neurons after traumatic injury to peripheral nerves are related to neuropathic pain symptoms. This study was conducted to elucidate the influence of nerve insult on stimulus-induced c-Fos expression and ERK phosphorylation by brainstem neurons. The brainstem trigeminal sensory nuclear complex (BTSNC) was examined for neuronal profiles immunolabeled with c-Fos and phosphorylated ERK (p-ERK) antibodies elicited by stimulation of the tongue with capsaicin after lingual or inferior alveolar nerve (IAN) injury. Abundant neuronal profiles immunolabeled for c-Fos and p-ERK elicited by capsaicin were distributed in the spinal trigeminal nucleus caudalis (Vc) without nerve injury. The spinal trigeminal nucleus oralis (Vo) contained limited numbers of these neuronal profiles after stimulation of the tongue. A significant reduction of these neuronal profiles in the ipsilateral Vc was detected after lingual nerve injury. After IAN injury, an increased number of neuronal profiles immunolabeled for c-Fos elicited by capsaicin was noted, while that of p-ERK was left unchanged in the ipsilateral Vc. On the both sides of the Vo, an increased number of capsaicin-induced neuronal profiles immunolabeled for c-Fos and p-ERK was detected after lingual or IAN injury. Differential effects of lingual or IAN injury on stimulus-induced c-Fos expression and ERK phosphorylation by Vo and Vc neurons may be involved in the complex nature of symptoms of trigeminal neuralgia.

THE CLINICAL PHENOTYPE OF IDIOPATHIC, SPONTANEOUS FACIAL PAIN DISEASE

The fifth and greatest cranial nerve, the trigeminal nerve (V), is in charge of detecting sensory inputs that come from the craniofacial region. The trigeminal ganglia house the cell bodies of the three branches of the nerve: the ophthalmic (V1), maxillary (V2), and mandibular (V3). These branches connect to second-order neurons in the trigeminal brainstem sensory nuclear complex. Trigeminal neuralgia is one of the most prevalent types of facial and cranial discomfort. Trigeminal neuralgia is characterized by abrupt, fleeting, and painful facial pain episodes in one or more of the V branches. As a result, the quality of life for those who suffer from the condition is drastically reduced.

Proceedings #21: Specific Patterns of Current Flow Generated by Different tDCS Montages in the Midbrain and in the Trigeminal Brainstem Sensory Nuclear Complex

Proceedings #21: Specific Patterns of Current Flow Generated by Different tDCS Montages in the Midbrain and in the Trigeminal Brainstem Sensory Nuclear Complex

Tooth pulp injury induces sex-dependent neuronal reshaping in the ventral posterolateral nucleus of the rat thalamus

Orofacial injuries often result in persistent pain and are therefore considered a common health problem worldwide. Considerable evidence suggests that peripheral sensory nerve injury results in diverse plastic changes in the central nervous system (CNS). Tooth pulp is innervated by trigeminal afferents which extend to the trigeminal brainstem sensory nuclear complex and send input to higher level neurons in the CNS, including the ventral posterolateral nucleus of the thalamus (VPL). In the present study, we examined the long term effects of pulpal injury on neuronal arborization in the VPL using morphological analysis via Golgi-Cox staining. In addition, we examined these effects in both male and female rats due to the major prevalence of oral pain in women. Quantitative morphological analysis revealed that pulpal injury induced neuronal hypertrophy in VPL neurons of female rats. In clear contrast, pulpal injury increased arborization close to the soma and reduced arborization distal to the soma without modification of total dendritic length in male rats. As a result, we show, for the first time, sex-dependent morphological alterations in VPL neurons after orofacial peripheral injury. Since dental injuries are readily reproducible in rat dental molars and closely mimic the clinical setting in humans, this model represents a useful tool to further understand mechanisms of orofacial pain.

Transdermal electrical neuromodulation of the trigeminal sensory nuclear complex improves sleep quality

Transdermal electrical neuromodulation of the trigeminal sensory nuclear complex improves sleep quality

Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex

The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms.Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model.Data from 13 healthy volunteers aged 19–46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (−3.7%, p = 0.009) and GABA (−10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling.Summarized, the present study indicates the applicability of 1H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain.

Distribution of hemokinin-1 in the rat trigeminal ganglion and trigeminal sensory nuclear complex

ObjectiveA new mammalian tachykinin peptide encoded in a TAC4 gene was identified and designated as hemokinin-1 (HK-1). A representative of the tachykinin peptide family is substance P (SP), and the function of SP has been well characterized as a pain transmitter or modulator, while it is possible that HK-1 is involved in pruriceptive processing, but, as yet, the distribution of HK-1 peptide in the trigeminal sensory system is still unknown. Thus, the aim of the present study was to elucidate the distribution of HK-1, while comparing the expression of SP, in the trigeminal ganglion and trigeminal sensory nuclear complex. DesignThe trigeminal ganglion and the brain stem of male SD rats were used in the immunohistochemical study. Since the amino acid sequence in the carboxyl-terminal regions of HK-1 and SP is common, polyclonal antibodies of HK-1 and SP derived from 6 amino acids consisting of amino-terminal regions of these peptides were produced in guinea pig and rabbit, respectively. The immunohistochemical staining of HK-1 and SP was conducted using frozen sections of the trigeminal ganglion and brain stem in rats. ResultsImmunohistochemical studies revealed the expression of HK-1 in small- and medium-sized trigeminal ganglion neurons, in the paratrigeminal nucleus, and in lamina I of the trigeminal nucleus caudalis, while there was no immunoreactivity of HK-1 in the trigeminal nucleus principalis, trigeminal nucleus oralis, and trigeminal nucleus interpolaris. ConclusionThese findings indicate that HK-1 is a target molecule for treatment of itch in the orofaicial regions.

In vivo magnetic resonance imaging at 11.7 Tesla visualized the effects of neonatal transection of infraorbital nerve upon primary and secondary trigeminal pathways in rats

Using 11.7T ultra high-field T2-weighted MRI, the present study aimed to investigate pathological changes of primary and secondary trigeminal pathways following neonatal transection of infraorbital nerve in rats. The trigeminal pathways consist of spinal trigeminal tract, trigeminal sensory nuclear complex, medial lemniscus, ventromedial portion of external medullary lamina and ventral posterior nucleus of thalamus. By selecting optimum parameters of MRI such as repetition time, echo time, and slice orientation, this study visualized the trigeminal pathways in rats without any contrast agents. Pathological changes due to the nerve transection were found at 8 weeks of age as a marked reduction of the areas of the trigeminal pathways connecting from the injured nerve. In addition, T2-weighted MR images of the trigeminal nerve trunk and the spinal trigeminal tract suggest a communication of CSF through the trigeminal nerve between the inside and outside of the brain stem. These results support the utility of ultra high-field MRI system for noninvasive assessment of effects of trigeminal nerve injury upon the trigeminal pathways.

Projections from the dorsal peduncular cortex to the trigeminal subnucleus caudalis (medullary dorsal horn) and other lower brainstem areas in rats

This study has revealed direct projections from the dorsal peduncular cortex (DP) in the medial prefrontal cortex (mPfC) to the trigeminal brainstem sensory nuclear complex and other lower brainstem areas in rats. We first examined the distribution of mPfC neurons projecting directly to the medullary dorsal horn (trigeminal subnucleus caudalis [Vc]) and trigeminal subnucleus oralis (Vo) which are known to receive direct projections from the lateral prefrontal cortex (insular cortex). After injections of the retrograde tracer Fluorogold (FG) into the rostro-dorsomedial part of laminae I/II of Vc (rdm-I/II-Vc), many neurons were labeled bilaterally (with an ipsilateral predominance) in the rostrocaudal middle level of DP (mid-DP) and not in other mPfC areas. After FG injections into the lateral and caudal parts of laminae I/II of Vc, or the Vo, no neurons were labeled in the mPfC. We then examined projections from the mid-DP by using the anterograde tracer biotinylated dextranamine (BDA). After BDA injections into the mid-DP, many axons and terminals were labeled bilaterally (with an ipsilateral predominance) in the rdm-I/II-Vc, periaqueductal gray and solitary tract nucleus, and ipsilaterally in the parabrachial nucleus and trigeminal mesencephalic nucleus. In addition, the connections of the mid-DP with the insular cortex were examined. Many BDA-labeled axons and terminals from the mid-DP were also found ipsilaterally in the caudalmost level of the granular and dysgranular insular cortex (GI/DI). After BDA injections into the caudalmost GI/DI, many axons and terminals were labeled ipsilaterally in the mid-DP. The projections from the mid-DP to the rdm-I/II-Vc and other brainstem nuclei suggest that mid-DP neurons may regulate intraoral and perioral sensory processing (including nociceptive processing) of rdm-I/II-Vc neurons directly or indirectly through the brainstem nuclei. The reciprocal connections between the mid-DP and caudalmost GI/DI suggest that this regulation may involve mid-DP interactions with the caudalmost GI/DI neurons.

The role of the trigeminal sensory nuclear complex in the pathophysiology of craniocervical dystonia.

Isolated focal dystonia is a neurological disorder that manifests as repetitive involuntary spasms and/or aberrant postures of the affected body part. Craniocervical dystonia involves muscles of the eye, jaw, larynx, or neck. The pathophysiology is unclear, and effective therapies are limited. One mechanism for increased muscle activity in craniocervical dystonia is loss of inhibition involving the trigeminal sensory nuclear complex (TSNC). The TSNC is tightly integrated into functionally connected regions subserving sensorimotor control of the neck and face. It mediates both excitatory and inhibitory reflexes of the jaw, face, and neck. These reflexes are often aberrant in craniocervical dystonia, leading to our hypothesis that the TSNC may play a central role in these particular focal dystonias. In this review, we present a hypothetical extended brain network model that includes the TSNC in describing the pathophysiology of craniocervical dystonia. Our model suggests the TSNC may become hyperexcitable due to loss of tonic inhibition by functionally connected motor nuclei such as the motor cortex, basal ganglia, and cerebellum. Disordered sensory input from trigeminal nerve afferents, such as aberrant feedback from dystonic muscles, may continue to potentiate brainstem circuits subserving craniocervical muscle control. We suggest that potentiation of the TSNC may also contribute to disordered sensorimotor control of face and neck muscles via ascending and cortical descending projections. Better understanding of the role of the TSNC within the extended neural network contributing to the pathophysiology of craniocervical dystonia may facilitate the development of new therapies such as noninvasive brain stimulation.

Reduction of Masticatory Neurons in the Tooth-extracted Mice: A Year-long Study

Background: It has been reported that the number of masticatory motor and sensory neurons were seriously diminished and the masseter muscles were severely atrophied in the genetically mutant osteopetrotic (op/op) mouse with no eruption of teeth and less-developed periodontal ligaments. The present study was designed to observe whether the sensory input from the periodontal mechanoreceptive afferents be involved in the development and maintenance of the masticatory system. Methods: A case-control study was carried out with 2 groups of male ICR mice. Unilateral extraction of upper and lower molars was carried out in the case group on day 20 after birth. For assessing effects of tooth loss on the masticatory neurons, both mice groups were sacrificed on days 30, 60, 90, 120, 180 and 360 after birth and the trigeminal mesencephalic neurons (Me5) and trigeminal ganglion (TG) were traced and counted on both sides of the central nervous System (CNS). Results: In case group, severe degeneration of the ipsilateral inferior alveolar nerve (IAN) was observed on as early as day 40 after birth and there was significant decrease in the number of labeled Me5 and TG neurons between 60th and 360th postnatal days on the tooth-extracted side. Labeled primary afferent terminals were also severely diminished in the trigeminal sensory nuclear complex (TSNC) on the tooth-extracted side. Conclusion: Present study suggests that the decrease in the sensory input due to the tooth loss causes the disorder of the development and maintenance of the masticatory system even in the normal animal. DOI: http://dx.doi.org/10.3329/cdcj.v10i2.16315 City Dent. Coll. J Volume-10, Number-2, July-2013

Neural Mechanisms That Underlie Angina-Induced Referred Pain in the Trigeminal Nerve Territory: A c-Fos Study in Rats.

The present study was designed to determine whether the trigeminal sensory nuclear complex (TSNC) is involved in angina-induced referred pain in the trigeminal nerve territory and to identify the peripheral nerve conducting nociceptive signals that are input into the TSNC. Following application of the pain producing substance (PPS) infusion, the number of Fos-labeled cells increased significantly in the subnucleus caudalis (Sp5C) compared with other nuclei in the TSNC. The Fos-labeled cells in the Sp5C disappeared when the left and right cervical vagus nerves were sectioned. Lesion of the C1-C2 spinal segments did not reduce the number of Fos-labeled cells. These results suggest that the nociceptive signals that conduct vagal afferent fibers from the cardiac region are input into the Sp5C and then projected to the thalamus.

P2X7 Receptor and Cytokines Contribute to Extra-territorial Facial Pain

The whisker pad area (WP) is innervated by the second branch of the trigeminal nerve and experiences allodynia and hyperalgesia following transection of the mental nerve (MN; the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain remain unclear. The ionotropic P2X7 ATP receptor (P2X7) in microglia is known to potentiate, via cytokines, the perception of noxious stimuli, raising the possibility that P2X7 and cytokines are involved in this extra-territorial pain. One day after MN transection (MNT), WP allodynia/hyperalgesia developed, which lasted for > 8 wks. Activation of microglia and up-regulation of P2X7, membrane-bound tumor necrosis factor (TNF)-α (mTNF-α), and soluble TNF-α (sTNF-α) in the trigeminal sensory nuclear complex (TNC) were evident for up to 6 wks after MNT. Allodynia/hyperalgesia after MNT was blocked by intracisternal administration of etanercept, a recombinant TNF-α receptor (p75)-Fc fusion protein. Intracisternal A438079, a P2X7 antagonist, also attenuated allodynia/hyperalgesia and blocked up-regulation of mTNF-α and sTNF-α in the TNC. We conclude that sTNF-α released by microglia following P2X7 activation may be important in both the initiation and maintenance of extra-territorial pain after MNT.

Myofascial Trigger Points in the Masticatory Muscles in Patients With and Without Chronic Mechanical Neck Pain

ObjectivesThe purpose of this study is to describe differences in the presence of masseter and temporalis muscle trigger points (TrPs) and jaw opening between individuals with mechanical neck pain and healthy controls. MethodsTwenty patients with mechanical neck pain (60% women) without symptoms in the orofacial region, aged 20 to 37 years old, and 20 matched controls participated. Temporalis and masseter muscles were examined for the presence of TrPs in a blinded design. Trigger points were considered active if the subject recognized the pain as a familiar symptom, whereas the TrPs was considered latent if the pain was not recognized as a symptom. Jaw opening was assessed with a ruler. ResultsA greater number (P < .001) of TrPs in the masticatory muscles were found in patients than in controls. None of the patients or healthy controls recognized the referred pain as familiar; thus, latent rather than active TrPs were found. The distribution of TrPs between groups was different for the masseter (left odds ratio [OR], 3.4; right OR, 8.1; P < .001) and temporalis (left OR, 2.8; right OR, 5.7; P < .001) muscles. Patients with neck pain had smaller jaw opening than controls (P < .001). A negative correlation between active jaw opening and the number of TrPs within the masticatory muscles (rs = −0.6; P < .001) was found: the greater the number of TrPs, the smaller the jaw opening. ConclusionsFor the subjects in this study, those with mechanical chronic neck pain had more latent TrPs in the masticatory muscles and reduced jaw opening compared to healthy controls. These findings may suggest the spread of sensitization from the cervical segment to the trigeminal brain stem sensory nuclear complex.

P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury

The present study directly addresses the roles of the P2X(7) receptor (P2X(7)R), an ionotropic adenosine triphosphate (ATP) receptor, and cytokines in the induction of orofacial pain following chronic constriction injury (CCI) of the infraorbital nerve (IoN). Rats were anesthetized, and ligatures of 4-0 chromic gut were tied around the IoN. A438079, a P2X(7)R antagonist or SB203580, a phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK) inhibitor, was infused intrathecally into CCI-treated rats. In another group of rats, 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP), a P2X(7) R agonist, was infused intrathecally with A438079, SB203580 or etanercept, a tumor necrosis factor (TNF)-α receptor-binding recombinant drug. CCI of the IoN induced tactile allodynia/hyperalgesia and up-regulation of P2X(7)R, membrane-bound TNF-α (mTNF-α) and soluble TNF-α (sTNF-α) in the trigeminal sensory nuclear complex (TNC). Tactile allodynia/hyperalgesia or up-regulation of mTNF-α and sTNF-α in the TNC following CCI of the IoN was inhibited by A438079. SB203580 also attenuated tactile allodynia/hyperalgesia or up-regulation of mTNF-α, but not the up-regulation of sTNF-α in the TNC. Treatment of rats with BzATP induced tactile allodynia/hyperalgesia and up-regulation of sTNF-α and p-p38 in the TNC. Tactile allodynia/hyperalgesia or up-regulation of sTNF-α following BzATP treatment was inhibited by SB203580 and etanercept. Based on these findings, phosphorylation of p38 MAPK via P2X(7)R may induce tactile allodynia/hyperalgesia, which is most likely mediated by sTNF-α released by microglia.

Somatotopic direct projections from orofacial areas of secondary somatosensory cortex to trigeminal sensory nuclear complex in rats

Little is known about the projections from the orofacial areas of the secondary somatosensory cortex (S2) to the pons and medulla including the second-order somatosensory neuron pools. To address this in rats, we first examined the distribution of S2 neurons projecting to the trigeminal principal nucleus (Vp) or oral subnucleus (Vo) of the trigeminal sensory nuclear complex (TSNC) after injections of a retrograde tracer, Fluorogold (FG), into five regions in the Vp/Vo which were responsive to stimulation of trigeminal nerves innervating the orofacial tissues. A large number of FG-labeled neurons were found with a somatotopic arrangement in the dorsal areas of S2 (orofacial S2 area). This somatotopic arrangement in the orofacial S2 area was shown to closely match that of the orofacial afferent inputs by recording cortical surface potentials evoked by stimulation of the trigeminal nerves. We then examined the morphology of descending projections from these electrophysiologically defined areas of the orofacial S2 to the pons and medulla after injections of an anterograde tracer, biotinylated dextranamine (BDA), into the areas. A large number of BDA-labeled axon fibers and terminals were seen only in some of the second-order somatosensory neuron pools, most notably in the contralateral TSNC, although the labeled terminals were not seen in certain rostrocaudal levels of the contralateral TSNC including the rostrocaudal middle level of the trigeminal interpolar subnucleus. The projections to the TSNC showed somatotopic arrangements in dorsoventral, superficial-deep and rostrocaudal directions. The somatotopic arrangements in the Vp/Vo closely matched those of the electrophysiologically defined central projection sites of the orofacial trigeminal afferents in the TSNC. The present results suggest that the orofacial S2 projects selectively to certain rostrocaudal levels of the contralateral TSNC, and the projections may allow the orofacial S2 to accurately modulate orofacial somatosensory transmission to higher brain centers including the orofacial S2 itself.

Distinct Development of the Trigeminal Sensory Nuclei in Platypus and Echidna

Both lineages of the modern monotremes have been reported to be capable of electroreception using the trigeminal pathways and it has been argued that electroreception arose in an aquatic platypus-like ancestor of both modern monotreme groups. On the other hand, the trigeminal sensory nuclear complex of the platypus is highly modified for processing tactile and electrosensory information from the bill, whereas the trigeminal sensory nuclear complex of the short-beaked echidna (Tachyglossus aculeatus) is not particularly specialized. If the common ancestor for both platypus and echidna were an electroreceptively and trigeminally specialized aquatic feeder, one would expect the early stages of development of the trigeminal sensory nuclei in both species to show evidence of structural specialization from the outset. To determine whether this is the case, we examined the development of the trigeminal sensory nuclei in the platypus and short-beaked echidna using the Hill and Hubrecht embryological collections. We found that the highly specialized features of the platypus trigeminal sensory nuclei (i.e. the large size of the principal nucleus and oral part of the spinal trigeminal nuclear complex, and the presence of a dorsolateral parvicellular segment in the principal nucleus) appear around the time of hatching in the platypus, but are never seen at any stage in the echidna. Our findings support the proposition that the modern echidna and platypus are derived from a common ancestor with only minimal trigeminal specialization and that the peculiar anatomy of the trigeminal sensory nuclei in the modern platypus emerged in the ornithorhynchids after divergence from the tachyglossids.

Masseter inflammation differentially regulates three nitric oxide synthases in the rat trigeminal subnucleus caudalis

ObjectiveThe aim of the present study was to evaluate changes in expression levels of three nitric oxide synthases (NOSs), namely inducible NOS (iNOS), neuronal NOS (nNOS) and endothelial NOS (eNOS), in the subnucleus caudalis of the trigeminal sensory nuclear complex (Vc) under experimental myositis conditions. DesignMale Sprague Dawley rats were injected with an inflammatory agent, complete Freund's adjuvant (CFA), or capsaicin in the masseter muscle. The brainstem region containing the Vc was extracted at both immediate (30 and 60min) and longer (1, 3, 7 days) time points to examine the changes in the three NOS protein levels via the Western blot technique. Subsequently, the RT-PCR experiments were carried out to verify the changes in iNOS mRNA. ResultsFollowing the injections of CFA, there were no significant changes in the level of the three NOS proteins at the immediate time points. However, there was a significant upregulation of iNOS mRNA and protein 3 days after CFA-induced inflammation. Neither nNOS nor eNOS showed significant changes in the protein level at any of the longer time points. Capsaicin injection in the masseter, which we recently reported to upregulate all three NOS at the immediate time points, did not result in significant changes at longer time points. ConclusionAcute and chronic muscle inflammation differentially modulates the expression of the three NOS in the Vc. These data suggest that the contribution of each NOS in craniofacial muscle pain processing under inflammatory conditions may be anticipated with distinct temporal profiles.

Fos protein-like immunoreactive neurons induced by electrical stimulation in the trigeminal sensory nuclear complex of rats with chronically injured peripheral nerve

The rat trigeminal sensory nuclear complex (TSNC) was examined for Fos protein-like immunoreactive (Fos-LI) neurons induced by electrical stimulation (ES) of the lingual nerve (LN) at 2 weeks after injury to the LN or the inferior alveolar nerve (IAN). Intensity-dependent increase in the number of Fos-LI neurons was observed in the subnucleus oralis (Vo) and caudalis (Vc) of the spinal trigeminal tract nucleus irrespective of nerve injury. The number of Fos-LI neurons induced by ES of the chronically injured LN at A-fiber intensity (0.1 mA) was significantly increased in the Vo but not the Vc. On the other hand, in rats with chronically injured IAN, the number of Fos-LI neurons induced by ES of the LN at C-fiber intensity (10 mA) was significantly increased in the Vc but not the Vo. These results indicated that injury of a nerve innervating intraoral structures increased the c-Fos response of Vo neurons to A-fiber intensity ES of the injured nerve. A similar nerve injury enhanced the c-Fos response of Vc neurons to C-fiber intensity ES of a spared uninjured nerve innervating an intraoral territory neighboring that of the injured nerve. The present result show that nerve injury causes differential effects on c-Fos expression in the Vo and Vc, which may explain complexity of neuropathic pain symptoms in clinical cases.

Somatotopic direct projections from orofacial areas of primary somatosensory cortex to pons and medulla, especially to trigeminal sensory nuclear complex, in rats

The primary somatosensory cortex (S1) projects to the thalamus and brainstem somatosensory nuclei and modulates somatosensory information ascending to the S1 itself. However, the projections from the S1 to the brainstem second-order somatosensory neuron pools have not been fully studied. To address this in rats, we first revealed the somatotopic representation of orofacial areas in the S1 by recording cortical surface potentials evoked by stimulation of the lingual, mental, infraorbital, and frontal nerves. We then examined the morphology of descending projections from the electrophysiologically defined orofacial S1 areas to the pons and medulla after injections of an anterograde tracer, biotinylated dextranamine (BDA), into the orofacial S1 areas. BDA-labeled axon terminals were seen mostly in the trigeminal sensory nuclear complex (TSNC) and had a strong contralateral predominance. They also showed a somatotopic arrangement in dorsoventral and superficial-deep directions within almost all rostrocaudal TSNC levels, and in a rostrocaudal direction within the trigeminal caudal subnucleus. In the principal nucleus (Vp) or oral subnucleus (Vo) of TSNC, the BDA-labeled axon terminals showed a somatotopic arrangement closely matched to that of the electrophysiologically defined projection sites of orofacial primary afferents; these projection sites were marked by injections of a retrograde tracer, Fluorogold (FG), into the Vp or Vo. The FG injections labeled a large number of S1 neurons, with a strong contralateral predominance, in a somatotopic manner, which corresponded to that presented in the electrophysiologically defined orofacial S1 areas. The present results suggest that the orofacial S1 projections to somatotopically matched regions of trigeminal second-order somatosensory neuron pools may allow the orofacial S1 to accurately modulate orofacial somatosensory transmission to higher brain centers including the orofacial S1 itself.